Thoracic impedance detection with blood resistivity compensation

ABSTRACT

This document discusses, among other things, a cardiac rhythm management device or other implantable medical device that uses thoracic impedance to determine how much fluid is present in the thorax, such as for detecting or predicting congestive heart failure, pulmonary edema, pleural effusion, hypotension, or the like. The thoracic fluid amount determined from the thoracic impedance is compensated for changes in blood resistivity, which may result from changes in hematocrit level or other factors. The blood-resistivity-compensated thoracic fluid amount can be stored in the device or transmitted to an external device for storage or display. The blood-resistivity-compensated thoracic fluid amount can also be used to adjust a cardiac pacing, cardiac resynchronization, or other cardiac rhythm management or other therapy to the patient. This document also discusses applications of the devices and methods for predicting or indicating anemia.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.12/139,948, filed Jun. 16, 2008, which is a continuation of U.S.application Ser. No. 10/921,503, filed Aug. 19, 2004, now U.S. Pat. No.7,387,610, the specifications of which are herein incorporated byreference.

TECHNICAL FIELD

This document pertains generally to implantable medical devices and moreparticularly, but not by way of limitation, to congestive heart failure(CHF) thoracic fluid detection and other thoracic impedance systems,devices, or methods that compensate or correct for changes in bloodresistivity.

BACKGROUND

Variations in how much fluid is present in a person's thorax can takevarious forms and can have different causes. Eating salty foods canresult in retaining excessive fluid in the thorax and elsewhere. Posturechanges can also affect the amount of thoracic fluid. For example,moving from supine to standing can shift intravascular fluid away fromthe thorax toward the lower extremities.

Another example is pulmonary edema, which results in buildup ofextravascular fluid in the lungs. In pulmonary edema, fluid accumulatesin extracellular spaces, such as the spaces between lung tissue cells.One cause of pulmonary edema is congestive heart failure (CHF), which isalso sometimes referred to as “chronic heart failure,” or as “heartfailure.” CHF can be conceptualized as an enlarged weakened portion ofheart muscle. The impaired heart muscle results in poor cardiac outputof blood. As a result of such poor blood circulation, blood tends topool in blood vessels in the lungs. This intravascular fluid buildup, inturn, results in the extravascular fluid buildup mentioned above. Insum, pulmonary edema can be one important condition associated with CHF.

Yet another example of thoracic fluid accumulation is pleural effusion,which is the buildup of extravascular fluid in the space between thelungs and the rib cage. Pleural effusion can also result from CHFbecause, as discussed above, intravascular fluid buildup can result inthe extravascular interstitial fluid buildup. The extravascular fluidbuildup of pulmonary edema can, in turn, result in the extravascularfluid buildup of pleural effusion.

CHF may also activate several physiological compensatory mechanisms.Such compensatory mechanisms are aimed at correcting the reduced cardiacoutput. For example, the heart muscle may stretch to increase itscontractile power. Heart muscle mass may also increase. This is referredto as “hypertrophy.” The ventricle may also change its shape as anothercompensatory response. In another example, a neuro-endocrine responsemay provide an adrenergic increase in heart rate and contraction force.The Renin-Angiotensin-Aldosterone-System (RAAS) may be activated toinduce vasoconstriction, fluid retention, and redistribution of bloodflow. Although the neuro-endocrine response is compensatory, it mayoverload the cardiovascular system. This may result in myocardialdamage, and may exacerbate CHF.

Diagnosing CHF may involve physical examination, electrocardiogram(ECG), blood tests, chest radiography, or echocardiography. Managing aCHF patient is challenging. CHF may require potent drugs. Moreover,treatment may be thwarted by the compensatory mechanisms, which mayrecompensate for the presence of the medical treatment. Therefore,treating CHF involves a delicate balance to properly manage thepatient's hemodynamic status in a state of proper compensation to avoidfurther degeneration.

However, this delicate balance between compensation and effective CHFtreatment is easily upset, even by seemingly benign factors, such ascommon medication (e.g., aspirin), physiological factors, excitement, orgradual progression of the disease. This may plunge the patient into adecompensation crisis, which requires immediate corrective action so asto prevent the deterioration of the patient's condition which, if leftunchecked, can lead to death. In sum, accurately monitoring the symptomsof CHF, such as thoracic fluid accumulation, is very useful for avoidingsuch a decompensation crisis and properly managing the CHF patient in astate of relative well-being.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsdescribe substantially similar components throughout the several views.Like numerals having different letter suffixes represent differentinstances of substantially similar components. The drawings illustrategenerally, by way of example, but not by way of limitation, variousembodiments discussed in the present document.

FIG. 1 is a block diagram illustrating generally one example of a systemthat provides a thoracic fluid amount indication that is adjusted tocompensate for a change in blood resistivity, if any.

FIG. 2 is a schematic illustration of one example in which portions ofthe system are implemented in an implantable cardiac rhythm management(CRM) or other implantable medical device (IMD).

FIG. 3 is a block diagram illustrating generally another example inwhich portions of the system are implemented in an implantable CRM orother IMD.

FIG. 4 is a flow chart illustrating generally one example of a method ofproviding a thoracic fluid amount indication that is compensated for anychanges in blood resistivity.

FIG. 5 is a flow chart illustrating generally one example of a method ofdetecting anemia using a blood impedance measurement performed by animplantable medical device.

DETAILED DESCRIPTION

The following detailed description includes references to theaccompanying drawings, which form a part of the detailed description.The drawings show, by way of illustration, specific embodiments in whichthe invention may be practiced. These embodiments, which are alsoreferred to herein as “examples,” are described in enough detail toenable those skilled in the art to practice the invention. Theembodiments may be combined, other embodiments may be utilized, orstructural, logical and electrical changes may be made without departingfrom the scope of the present invention. The following detaileddescription is, therefore, not to be taken in a limiting sense, and thescope of the present invention is defined by the appended claims andtheir equivalents.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one. In this document, the term“or” is used to refer to a nonexclusive or, unless otherwise indicated.Furthermore, all publications, patents, and patent documents referred toin this document are incorporated by reference herein in their entirety,as though individually incorporated by reference. In the event ofinconsistent usages between this document and those documents soincorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

In this document, the term intravascular includes the term intracardiac.

In this document, the term cardiovascular includes an association witheither the heart or a blood vessel.

In this document, the term “thorax” refers to a human subject's bodyother than the subject's head, arms, and legs.

FIG. 1 is a block diagram illustrating generally one example of a system100 that provides an indication of the amount of fluid in the thorax(“thoracic fluid indication”) that is adjusted to compensate for achange in blood resistivity, if any. In this example, the system 100includes a thoracic impedance measurement circuit 102. The thoracicimpedance measurement circuit 102 receives at least one electricalsignal from electrodes associated with a patient's thorax. Thiselectrical signal is typically received in response to a test energyapplied to the thorax, such as by a thoracic impedance test energydelivery circuit 104.

One illustrative example of some electrode configurations and circuitsfor performing thoracic impedance measurements is described in Hartleyet al. U.S. Pat. No. 6,076,015 entitled RATE ADAPTIVE CARDIAC RHYTHMMANAGEMENT DEVICE USING TRANSTHORACIC IMPEDANCE, which is assigned toCardiac Pacemakers, Inc., and which is incorporated herein by referencein its entirety, including its description of performing thoracicimpedance measurements. The Hartley et al. U.S. Pat. No. 6,076,015 usesthoracic impedance to obtain a respiration signal. By contrast, thepresent patent application uses thoracic impedance to obtain a thoracicfluid status signal. Therefore, the signal of interest in the presentpatent application would be deemed noise in the Hartley et al. U.S. Pat.No. 6,076,015, and vice-versa. However, both thoracic fluid status andrespiration are obtainable using the thoracic impedance detectiontechniques described in the Hartley et al. U.S. Pat. No. 6,076,015. Thepresent thoracic fluid status signal of interest is obtained from alower frequency (i.e., a “near-DC”) portion of the thoracic impedancesignal rather than the frequencies of the respiration signal describedin the Hartley et al. U.S. Pat. No. 6,076,015. In this document, the“near-DC” component of the thoracic impedance signal refers to thefrequencies below which respiration and cardiac contractionssignificantly influence the thoracic impedance signal. This near-DCcomponent of the thoracic impedance signal, therefore, typically refersto signal frequencies below a cutoff frequency having a value of about0.1 Hz, such as at signal frequencies between about 5×10⁻⁷ Hz and 0.05Hz, because the cardiac stroke and respiration components of thethoracic impedance signal lie at higher frequencies. Fluid accumulationin the thorax corresponds to a decrease in the near-DC thoracicimpedance. Conversely, fluid depletion in the thorax corresponds to anincrease in the near-DC thoracic impedance. As discussed above, fluidaccumulation may result from, among other things, pulmonary edema orpleural effusion, both of which may result from CHF.

In the example of FIG. 1, the system 100 also includes a controller 108.The controller 108 is typically a microprocessor or any other circuitthat is capable of sequencing through various control states such as,for example, by using a digital microprocessor having executableinstructions stored in an associated instruction memory circuit, amicrosequencer, or a state machine. In this example, the controller 108includes a digital signal processor (DSP) circuit 110. The digitalsignal processor circuit 110 performs any digital filtering or othersignal processing needed to extract from the thoracic impedance signal anear-DC desired thoracic fluid amount signal. The digital signalprocessor circuit 110, therefore, may implement one or more filtercircuits, and such filter circuits may be implemented as a sequence ofexecutable instructions, rather than by dedicated filtering hardware.

However, the present inventors have recognized that the near-DC thoracicimpedance signal is typically also affected by confounding factors otherthan the amount of fluid present in the thorax. One such confoundingfactor is any change in blood resistivity. Blood resistivity changes asa function of hematocrit in the blood. The hematocrit (Ht) or packedcell volume (PCV) is the proportion of blood that is occupied by redblood cells. It is typically between 0.35 and 0.52, and is slightlyhigher on average in males than in females. For example, when a patientis dehydrated, there will be less fluid in the patient's blood.Therefore, the patient's hematocrit level will increase, that is, thepatient's blood will include a higher percentage of other components,such as insulative red blood cells. This will increase the bloodresistivity, which, in turn, will affect the thoracic impedance signaleven through it is not necessarily associated with the extravascularfluid accumulation of pulmonary edema or pleural effusion. Other factorsthat are believed to possibly influence blood resistivity include thepatient's electrolyte level, certain medications in the blood, proteinsin the blood, or blood gas concentrations.

As an illustrative example, the above change in hematocrit percentagefrom 35% to 52% may correspond to a change in resistivity from about 140Ω·cm to about 200 Ω·cm. Such changes in blood resistivity will influencethe near-DC thoracic impedance measurement. This will confound anextravascular thoracic fluid amount determination using the near-DCthoracic impedance measurement, unless the extravascular thoracic fluidamount determination is corrected for such variations in bloodresistivity, if any. Measurement of variations in blood resistivity istypically affected by the frequency of the excitation signal that areused. At higher excitation frequencies, blood cells typically becomemore resistive.

Accordingly, the system in FIG. 1 illustrates a blood resistivitymeasurement circuit 106. The blood impedance measurement circuit 106receives a blood impedance measurement from electrodes that areassociated with blood (and preferably blood in the thorax) such as inresponse to a delivery of test energy by a blood impedance test energydelivery circuit 112. In one example, the blood impedance measurementcircuit 106 and the blood impedance test energy delivery circuit 112 areconfigured similar to the thoracic impedance measurement circuit 102 andthe thoracic impedance test energy delivery circuit 104, respectively,as discussed above, except for being connected to different electrodes.Using the blood impedance measurement, the controller 108 executes asequence of instructions to compute a blood resistivity correction 114.The blood resistivity correction 114 is applied to the thoracic fluidindication that is output by the digital signal processor circuit 110.This yields an adjusted thoracic fluid amount indication 116.

In FIG. 1, the thoracic impedance test energy delivery circuit 104 isillustrated separately from the blood impedance test energy deliverycircuit 112 to assist the reader's conceptualization. In practice, thesecircuits, or portions thereof, may be combined. The combined circuit maybe coupled to different electrodes for delivering the thoracic impedancetest energy than for delivering the blood impedance test energy.Similarly, in FIG. 1, the thoracic impedance measurement circuit 102 isillustrated separately from the blood impedance test energy deliverycircuit 112 to assist the reader's conceptualization. In practice, thesecircuits, or portions thereof, may be combined. The combined circuit maybe coupled to different electrodes for measuring the responsive voltagesfor the thoracic and blood impedance measurements, as discussed below.

FIG. 2 is a schematic illustration of one example in which portions ofthe system 100 are implemented in an implantable cardiac rhythmmanagement (CRM) or other implantable medical device (IMD) 200. In thisexample, the IMD 200 is coupled to a heart 202 using at least oneleadwire, such as a multielectrode leadwire 204. In this example, theleadwire 204 includes a tip electrode 206, a distal ring electrode 208,and a proximal ring electrode 210, each of which is disposed in theright ventricle of the heart 202. In this example, each of the tipelectrode 206, the distal ring electrode 208, and the proximal ringelectrode 210 is independently electrically connected to a correspondingseparate electrically conductive terminal within an insulating header212. The header 212 is affixed to a housing 214 carrying electroniccomponents of the IMD 200. In this example, the header 212 includes aheader electrode 216, and the housing 214 includes a housing electrode218.

In one example, thoracic impedance is sensed by delivering a testcurrent between: (1) at least one of the ring electrodes 208 or 210; and(2) the housing electrode 218, and a resulting responsive voltage ismeasured across the tip electrode 206 and the header electrode 216.Because the IMD 200 is typically pectorally implanted at some distanceaway from the heart 202, this electrode configuration injects the testcurrent over a substantial portion (but typically not the entireportion) of the patient's thorax, such that when the resulting voltagemeasurement is divided by the test current magnitude, it yields anindication of thoracic impedance. Using different electrodes fordelivering the current and for measuring the responsive voltage reducesthe component of the measured impedance signal that results from ohmiclosses in the leadwires to the test current delivery electrodes. Whilesuch a “four-point” probe is useful, it is not required. In otherexamples, a “three-point probe” (having three electrodes, with oneelectrode used for both test current delivery and responsive voltagemeasurement), or a “two-point probe” (having two electrodes, eachelectrode used for both test current delivery and responsive voltagemeasurement) are used. Moreover, other electrode combinations couldalternatively be used to implement a four-point probe. The abovefour-point probe description provides an illustrative example of onesuitable four-point probe configuration.

In one example, blood impedance is sensed by delivering a test currentbetween: (1) one of the distal ring electrode 208 or the proximal ringelectrode 210; and (2) the housing electrode 218. A resulting responsivevoltage is measured between: (1) the other of the distal ring electrode208 or the proximal ring electrode 210; and (2) the tip electrode 206.In this example, although the test current is injected across asubstantial portion of the patient's thorax, as discussed above, theresponsive voltage signal of interest is measured across electrodeswithin the same chamber of the patient's heart (or, alternatively,within the same blood vessel). Therefore, when the responsive voltagemeasurement is divided by the test current magnitude, it yields anindication of the blood impedance in the heart chamber rather than thethoracic impedance. The measured blood impedance is used to compensatethe measured thoracic impedance for changes in the blood impedance.

FIG. 3 is a block diagram illustrating generally another example inwhich portions of the system 100 are implemented in an implantable CRMor other IMD 300. The example of FIG. 3 includes an impedance teststimulus circuit 302 that, together with an impedance measurementcircuit 304, provides thoracic and blood impedance measurements. Inresponse to one or more control signals from the controller 108, anelectrode configuration multiplexer 306 couples these circuits to theappropriate electrodes for the particular thoracic or blood impedancemeasurement. In this example, the multiplexer 306 is also coupled to aheart signal sensing circuit 308, which includes sense amplifier orother circuits for detecting from particular electrodes intrinsicelectrical heart signals that include electrical depolarizationscorresponding to heart contractions. The multiplexer 306 is also coupledto a therapy circuit 310, such as a pulse delivery circuit fordelivering pacing, cardioversion, or defibrillation energy to particularelectrodes in response to one or more control signals received from thecontroller 108.

In the example of FIG. 3, the DSP circuit 110 processes the thoracicimpedance measurements from the impedance measurement circuit 304. TheDSP circuit 110 extracts a cardiac stroke signal or a respiration signalfrom the thoracic impedance signal, such as by using techniquesdescribed in the above-incorporated Hartley et al. U.S. Pat. No.6,076,015. One or both of the extracted cardiac stroke or respirationsignals is provided to a blood impedance measurement synchronizationcircuit 312. The synchronization circuit 312 includes one or morepeak-detector, level-detector, or zero-cross detector circuits tosynchronize the blood impedance measurement to the same sample point ofa cardiac contraction cycle or a respiration cycle. This reduces theeffect of variations in one or both of these cycles on the bloodimpedance measurement. Similarly, the measurements can be taken underthe same conditions with respect to posture or circadian cycle to reducethose effects on the blood impedance measurement. Posture can bedetected using an accelerometer or other posture sensor; circadian cyclecan be ascertained from a time-of-day indication provided by a clockcircuit within the controller 108. Alternatively, the cardiac cycleinformation is extracted from the heart signal sensing circuit 308,either by itself or in combination with information from the controller108 about when pacing or other stimulus pulses that evoke a responsiveheart contraction are issued. The controller 108 computes an adjustedthoracic fluid indication 116 from the measured thoracic impedance. Theadjusted thoracic fluid indication 116 is compensated for bloodresistivity variations using the blood resistivity correction 114obtained using the measured blood impedance. In a further example, theimplantable medical device 300 includes a telemetry circuit 314 thatcommunicates one of the blood-resistivity-compensated thoracic impedanceor the blood resistivity and thoracic impedance measurements to anexternal programmer 316 or the like for further processing, storage, ordisplay.

FIG. 4 is a flow chart illustrating generally one example of a method ofproviding a thoracic fluid amount indication that is compensated for anychanges in blood resistivity. At 400, a thoracic impedance is detected.This may be accomplished in a number of different ways. In oneillustrative example, such as described in Hartley et al. U.S. Pat. No.6,075,015, it includes injecting a four-phase carrier signal, such asbetween a housing electrode 218 and a ring electrode 208. In thisexample, the first and third phases are +320 microampere pulses that are20 microseconds long. The second and fourth phases are −320 microamperepulses that are 20 microseconds long. The four phases are repeated at 50millisecond intervals to provide a carrier test current signal fromwhich a responsive voltage can be measured. However, as discussedelsewhere in this document, because blood resistivity varies withexcitation frequency, a different excitation frequency may also be used.

The Hartley et al. U.S. Pat. No. 6,075,015 describes an exciter circuitfor delivering such a test current stimulus (however, the present systemcan alternatively use other suitable circuits, including an arbitrarywaveform generator that is capable of operating at different frequenciesor of mixing different frequencies to generate an arbitrary waveform).It also describes a signal processing circuit for measuring a responsivevoltage between a housing electrode 216 and a tip electrode 206. In oneexample, the signal processing circuit includes a preamplifier,demodulator, and bandpass filter for extracting the thoracic impedancedata from the carrier signal, before conversion into digital form by anA/D converter. Further processing is performed digitally, and isperformed differently in the present system 100 than in the Hartley etal. U.S. Pat. No. 6,075,015.

For example, the Hartley et al. U.S. Pat. No. 6,075,015 includes abandpass filter that receives the output of the A/D converter. Thepurpose of the highpass portion of the bandpass filter is to attenuatethe near-DC portion of the thoracic impedance signal, which is thesignal of interest to the present system 100. Therefore, the presentsystem 100 eliminates the highpass filter. The cutoff frequency of theremaining lowpass filter is selected to pass the near-DC portion of thethoracic impedance signal and attenuate higher frequency portions of thethoracic impedance signal, including the respiration and cardiac strokecomponents of the thoracic impedance signal. In one example, aprogrammable cutoff frequency lowpass filter is used. In anotherexample, an adaptive cutoff frequency lowpass filter is used, such thatthe cutoff frequency is moved to a higher frequency for higher values ofheart rate and respiration frequency, and the cutoff frequency is movedto a lower frequency for lower values of heart rate and respirationfrequency.

At 402 of FIG. 4, blood impedance is detected and measured. There are anumber of ways in which this can be done. In one example, the bloodimpedance measurement is performed in the same manner as the thoracicimpedance measurement, except that measurement of the responsive voltageis across two electrodes that are both typically located in the sameheart chamber or same blood vessel, such as between (1) one of thedistal ring electrodes 208 or the proximal ring electrode 210; and (2)the other of the distal ring electrode 208 or the proximal ringelectrode 210. Because the blood impedance is to be used to correct athoracic fluid indication, it is typically detected and measured at ornear the thorax. Alternatively, however, even an external bloodimpedance measurement could be used, if desired. In one example, theblood impedance is sampled under appropriate other conditions (e.g., ata like point in different cardiac cycles, at a like point in differentrespiration cycles, etc.).

At 404, a thoracic fluid amount indication is determined. There are anumber of ways in which this can be done. In one example, the thoracicfluid amount indication is given by the value of the near-DC thoracicimpedance signal, which may be averaged or otherwise filtered, ifdesired. In another example, a baseline value of this averaged orotherwise filtered near-DC thoracic impedance signal is obtained fromthe patient, and the thoracic fluid amount indication is given by thedifference of the near-DC thoracic fluid impedance value (with the sameor different averaging or filtering) from this baseline value.

At 406, the thoracic fluid amount indication obtained from the near-DCthoracic impedance is adjusted to compensate for changes in bloodresistivity. In one example, the adjusted thoracic fluid amountindication is given by:TFA_(adj)=TFA_(raw)·(ρ_(Blood, current))÷(ρ_(Blood, baseline)). In thisequation, TFA_(adj) is the adjusted value of the thoracic fluid amount,(ρ_(Blood, baseline)) is the baseline value of the blood resistivity,and (ρ_(Blood, current)) is the current value of the blood resistivity.In the present case, since the same electrodes are used for both thebaseline and current blood resistance measurements, the resistivityratio (ρ_(Blood, current))÷(ρ_(Blood, baseline)) is given by thecorresponding ratio of the blood resistances, i.e.,(Z_(Blood, current))÷(Z_(Blood, baseline)).

In a further example, such as where the implantable medical device 300optionally includes a posture sensor or detector 318, a separatebaseline impedance or resistivity is provided for different postures,since posture affects thoracic impedance measurements. In one example, aseparate baseline impedance or resistivity is stored for uprightpostures (e.g., sitting or standing) than for recumbent postures (e.g.,supine, prone, left lateral decubitus, right lateral decubitus). In afurther example, a separate baseline impedance or resistivity is storedfor one or more of the different subtypes of upright or recumbentpostures. In compensating the thoracic fluid amount indication, theposture compensation module 320 compensates a particular resistivitymeasurement by using a baseline resistivity that corresponds to thethen-current posture indicated by the postures detector 318. One exampleof a suitable posture detector 318 is a commercially available two-axisaccelerometer, such as Model No. ADXL202E, manufactured by AnalogDevices, Inc. of Norwood, Mass., USA.

The compensated thoracic fluid amount indication can be stored in theimplantable medical device 300 or transmitted to the external device316. Moreover, in one example, the implantable medical device 300 orexternal device 316 is capable of storing a history of the values of thethoracic fluid amount indication to assist the physician in managing theCHF state of the patient. In one example, the external device 316 iscapable of displaying a graph, histogram or other chart of such thoracicfluid amount values.

In a further example, the implantable medical device 300 or the externaldevice 316 determines whether heart failure decompensation, pulmonaryedema, or pleural effusion is present, such as by comparing an increasein the blood-resistivity-compensated thoracic fluid amount indication toa corresponding first threshold value to deem one or more of theseconditions to be present.

In yet a further example, the implantable medical device 300 or theexternal device 316 predicts whether heart failure decompensation,pulmonary edema, or pleural effusion is likely to become present in thefuture, such as by comparing an increase in theblood-resistivity-compensated thoracic fluid amount indication to acorresponding second threshold value to deem one or more of theseconditions to be likely in the future. The second threshold used for thecondition prediction may be different from the first threshold used forthe condition detection. In one example, the second threshold valuereflects a smaller increase in the thoracic fluid amount indication thanthe first threshold value.

In yet a further example, the implantable medical device 300 adjusts atherapy to the patient using the thoracic fluid amount indication. Inone example, an increase in the thoracic fluid amount indicationtriggers an increase in a rate at which pacing pulses are delivered tothe heart. In another example, a change in the thoracic fluid amountindication results in altering another programmable parameter of cardiacpacing or cardiac resynchronization therapy, such as, for example,atrioventricular (AV) delay, particular cardiac stimulation sites,interventricular delay, or intraventricular delay. In a further example,a change in the thoracic fluid amount indication triggers the providingof a warning or other indication to the patient to adjust a medicationlevel (for example, a diuretic).

Another application for the present systems, devices, and methods is inanemia detection. Anemia is a pathological condition that is oftenpresent in CHF patients. Diagnosing and treating anemia will improve apatient's cardiac function. Therefore, there is a need to detect anemiain CHF patients, for example, to communicate a diagnosis regarding theanemia status to a CHF patient's health care provider.

FIG. 5 is a flow chart illustrating generally one example of an anemiadetection method. At 500, a baseline blood impedance is established. Inone example, this includes obtaining one or more near-DC blood impedancemeasurements (typically taken within the same blood vessel or heartchamber) such as described above with respect to 402 of FIG. 4. In oneexample, the baseline blood impedance is established by computing acentral tendency (e.g., average, median, low-pass filtered, etc.) valueof a series of such measured blood impedances over a desired timeinterval (for example, one month).

At 502, a current blood impedance is measured. This near-DC bloodimpedance measurement is typically performed in the same manner andlocation as described above for establishing the baseline. At 504, thecurrent blood impedance is compared to the baseline blood impedance. Asdescribed above, a higher percentage of red blood cells tends toincrease blood impedance. Therefore, when the current blood impedancefalls far enough below the baseline blood impedance, then anemia may beindicated. Therefore, in one example, if the current blood impedancefalls below the baseline blood impedance by at least an offset thresholdvalue, then anemia is declared to be present at 506. In one example, theoffset value is a fixed or programmable percentage of the baseline bloodimpedance (e.g., 5%, 10%, 20%, etc.). The offset value is typically setto prevent normal physiological variations in blood impedance fromtriggering an anemia detection. In another example, such as by choosinga different threshold value, the comparison predicts that anemia islikely to occur (e.g., if the blood impedance falls at least 10% belowits baseline value, then future anemia is predicted; if the bloodimpedance then falls at least 20% below its baseline value, then presentanemia is declared).

In one further example, if anemia is predicted or declared present, thatinformation is telemetered or otherwise communicated to the patient'shealth care provider from the implantable medical device, such as byproviding such information to an external device for storage or display.In one example, such communication takes place the next time that theimplantable medical device is interrogated by a programmer or otherexternal interface. In another example, such the implantable medicaldevice itself initiates a telemetric or other communication of suchinformation to an external device. In yet a further example, an anemiawarning is provided to the patient, either directly by the implantablemedical device (e.g., an audible warning), or via an external interfacedevice.

As discussed above, measurement of variations in blood resistivity istypically affected by the frequency of the excitation signal that areused. At higher excitation frequencies, blood cells typically becomemore resistive. Therefore, to yield a more sensitive measurement ofanemia, it may be desirable to use a higher excitation frequency thanwould be used for detecting thoracic impedance, and for correcting theresulting thoracic impedance measurements for changes in bloodresistivity. Alternatively, such as for measuring thoracic fluid status,if a change in blood resistivity exceeds a certain threshold value then,in one example, the system automatically switches to a lower excitationfrequency that is affected less by changes in blood resistivity.

Although much of the above discussion has emphasized correcting near-DCthoracic impedance measurements to account for changes in bloodresistivity, hematocrit-related blood resistivity changes may alsoaffect higher frequency components of the thoracic impedance signal(e.g., respiration components, cardiac stroke components, etc.),somewhat analogous to the way in which patient posture can affect suchhigher frequency components of the thoracic impedance signal. Aspects ofthe present blood resistivity measurement and correction techniques mayalso be used for correcting such higher-frequency components of thethoracic impedance signal. However, the effects of blood resistivitychanges at higher frequency may be nonlinear, making correction with asingle multiplicative correction factor difficult or impossible.Therefore, a nonlinear correction function may be used, if needed. Sucha nonlinear correction function may be empirically determined. In oneexample, the nonlinear correction function may be implemented as alookup table. Moreover, the higher-frequency components of the thoracicimpedance signal may be used to infer thoracic fluid status even much ofthe above discussion focused on particular examples that extract athoracic fluid status signal from the near-DC component of the thoracicimpedance signal.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. Many other embodiments will be apparent to those of skill inthe art upon reviewing the above description. The scope of the inventionshould, therefore, be determined with reference to the appended claims,along with the full scope of equivalents to which such claims areentitled. In the appended claims, the terms “including” and “in which”are used as the plain-English equivalents of the respective terms“comprising” and “wherein.” Also, in the following claims, the terms“including” and “comprising” are open-ended, that is, a system, device,article, or process that includes elements in addition to those listedafter such a term in a claim are still deemed to fall within the scopeof that claim. Moreover, in this document and in the following claims,the terms “first,” “second,” and “third,” etc. are used merely aslabels, and are not intended to impose numerical requirements on theirobjects.

1. A method comprising: obtaining a first blood resistivity quantityduring a first time using at least one implanted intravascular orintracardiac electrode in a subject; obtaining a second bloodresistivity quantity during a second time using the at least oneimplanted intravascular or intracardiac electrode; comparing the secondblood resistivity quantity to the first blood resistivity quantity; anddeclaring an indication or prediction of anemia to be present in thepatient when the second blood resistivity quantity is less than thefirst blood resistivity quantity by at least a first amount.
 2. Themethod of claim 1, wherein obtaining the first blood resistivityquantity and obtaining the second blood resistivity quantity areperformed in the same blood vessel or heart chamber.
 3. The method ofclaim 1, wherein obtaining the first blood resistivity quantity andobtaining the second blood resistivity quantity are performed under alike condition with respect to at least one of a cardiac cycle, arespiratory cycle, a posture, and a circadian cycle.
 4. The method ofclaim 1, comprising communicating an indication of anemia predicted oranemia present to an external device.
 5. The method of claim 1, whereindeclaring an indication or prediction of anemia includes: declaring anindication of anemia to be present in the patient when the second bloodresistivity quantity is less than the first blood resistivity quantityby at least a second amount; and declaring a prediction of anemia to bepresent in the patient when the second blood resistivity quantity isless than the first blood resistivity quantity by at least the firstamount and by less than the second amount.
 6. The method of claim 1,comprising communicating information regarding the indication orprediction of anemia.
 7. The method of claim 1, comprising displayinginformation regarding the indication or prediction of anemia.
 8. Themethod of claim 7, wherein displaying the information includesdisplaying the information using an external device.
 9. The method ofclaim 1, comprising providing an anemia warning with the indication orprediction of anemia.
 10. The method of claim 1, wherein at least oneof: obtaining the first blood resistivity quantity includes detecting afirst blood resistivity measurement during the first time; or obtainingthe second blood resistivity quantity includes detecting a second bloodresistivity measurement during the second time.
 11. The method of claim1, wherein at least one of: obtaining the first blood resistivityquantity includes combining two or more first blood resistivitymeasurements acquired during the first time; or obtaining the secondblood resistivity quantity includes combining two or more second bloodresistivity measurements acquired during the second time.
 12. The methodof claim 1, wherein at least one of: obtaining the first bloodresistivity quantity includes averaging two or more first bloodresistivity measurements acquired during the first time; or obtainingthe second blood resistivity quantity includes averaging two or moresecond blood resistivity measurements acquired during the second time.13. An implantable medical device comprising: a blood resistivitymeasurement circuit configured to provide a blood resistivity signalusing first and second electrodes; a controller coupled to the bloodresistivity measurement circuit, the controller configured to determinean indication or prediction of anemia by comparing a second bloodresistivity quantity to an earlier first blood resistivity quantity; anda communication circuit coupled to the controller, the communicationcircuit configured to communicate the indication or prediction of anemiato an external interface device.
 14. The implantable medical device ofclaim 13, wherein the first and second electrodes are located within thesame blood vessel or heart chamber.
 15. The implantable medical deviceof claim 13, wherein the first and second electrodes are included on aleadwire.
 16. The implantable medical device of claim 15, wherein thefirst electrode includes a ring electrode and the second electrodeincludes a tip electrode.
 17. The implantable medical device of claim15, comprising: a third electrode included on a housing of theimplantable medical device; and a fourth electrode included on theleadwire; a test current circuit configured to deliver a test currentbetween the third and fourth electrodes; and a voltage measurementcircuit configured to measure a resulting voltage between the first andsecond electrodes.
 18. The implantable medical device of claim 17,wherein the fourth electrode includes a ring electrode.
 19. Theimplantable medical device of claim 13, comprising a heart signalsensing circuit configured to synchronize the first and second times tolike portions of different cardiac cycles.
 20. The implantable medicaldevice of claim 13, comprising a posture sensor and a posturecompensation module configured to store different first bloodresistivity quantities corresponding to different postures obtained fromthe posture sensor.
 21. The implantable medical device of claim 13,comprising a thoracic impedance measurement circuit configured tosynchronize the first and second times to like portions of differentrespiration cycles.
 22. The implantable medical device of claim 13,wherein at least one of: the first blood resistivity quantity includes afirst blood resistivity measurement detected during the first time; orthe second blood resistivity quantity includes a second bloodresistivity measurement detected during the second time.
 23. Theimplantable medical device of claim 13, wherein at least one of: thefirst blood resistivity quantity includes a combination of two or morefirst blood resistivity measurements acquired during the first time; orthe second blood resistivity quantity includes a combination of two ormore second blood resistivity measurements acquired during the secondtime.
 24. The implantable medical device of claim 13, wherein at leastone of: the first blood resistivity quantity includes an average of twoor more first blood resistivity measurements acquired during the firsttime; or the second blood resistivity quantity includes an average oftwo or more second blood resistivity measurements acquired during thesecond time.
 25. A system comprising: means for obtaining a first bloodresistivity quantity during a first time using at least one implantedintravascular or intracardiac electrode in a subject; means forobtaining a second blood resistivity quantity during a second time usingthe at least one implanted intravascular or intracardiac electrode;means for comparing the second blood resistivity quantity to the firstblood resistivity quantity; and means for declaring an indication orprediction of anemia to be present in the patient when the second bloodresistivity quantity is less than the first blood resistivity quantityby at least a first amount.
 26. The system of claim 25, wherein themeans for declaring the indication or prediction of anemia includes:means for declaring an indication of anemia to be present in the patientwhen the second blood resistivity quantity is less than the first bloodresistivity quantity by at least a second amount; and means fordeclaring a prediction of anemia to be present in the patient when thesecond blood resistivity quantity is less than the first bloodresistivity quantity by at least the first amount and by less than thesecond amount.
 27. The system of claim 25, comprising means forcommunicating information regarding the indication or prediction ofanemia.
 28. The system of claim 25, wherein at least one of: the meansfor obtaining the first blood resistivity quantity includes means fordetecting a first blood resistivity measurement during the first time;or the means for obtaining the second blood resistivity quantityincludes means for detecting a second blood resistivity measurementduring the second time.
 29. The system of claim 25, wherein at least oneof: the means for obtaining the first blood resistivity quantityincludes means for combining two or more first blood resistivitymeasurements acquired during the first time; or the means for obtainingthe second blood resistivity quantity includes means for combining twoor more second blood resistivity measurements acquired during the secondtime.
 30. The system of claim 25, wherein at least one of: the means forobtaining the first blood resistivity quantity includes means foraveraging two or more first blood resistivity measurements acquiredduring the first time; or the means for obtaining the second bloodresistivity quantity includes means for averaging two or more secondblood resistivity measurements acquired during the second time.